Protection is Never Premature: Maternal COVID-19 Infection is Associated with Adverse Perinatal Outcomes

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INFECTIOUS DISEASE

Medical writer: Christy Leung | Last updated: 5 December 2022 | In: COVID-19, SARS-CoV2, Infectious Disease, Paediatric

Article Keywords

paediatrics, Infectious Disease, obstetrics, COVID-19, SARS-CoV-2

Pregnancy can be divided into three trimesters, corresponding to different stages of foetal development — the first trimester (Weeks 0 to 13+6) is characterised by foetal organ growth including neurodevelopment and craniofacial development^1,2; developed organs gain functionality during the second trimester (Weeks 14 to 26+6) and the foetus grows further and prepares for viability at the third trimester (Weeks 27 to 40+6).^1,2 This article aims to explore the association between maternal coronavirus disease 2019 (COVID-19) infection of any timing, severity and causative viral (SARS-CoV-2) variant with foetal or perinatal outcomes, including stillbirth (at ≤20 weeks of gestation), preterm birth (at ≤37 weeks of gestation) and neonatal respiratory distress.^3,4

Literature findings on first trimester maternal COVID-19 infection consequences are diverged. A study by Cosma et al included subjects diagnosed by serial seromolecular testing and revealed that infection during the first trimester did not significantly worsen perinatal outcomes — neonatal birth weight, Apgar score or umbilical artery pH values were comparable among the children born to SARS-CoV-2-positive women (case group) and those born to SARS-CoV-2-negative women (control group).⁵ No neonates were tested positive for SARS-CoV-2 at the time of delivery; in fact, IgG SARS-CoV-2 antibodies were detected in the arterial cord blood samples of case group newborns, supporting earlier evidence of placenta IgG transfer for additional neonatal protection.⁶ Compared to 8 out of 105 (7.6%) control group newborns, 2 out of 16 (12.5%) neonates in the case group experienced neonatal complications (p=0.86) defined as Apgar score ≤7 at 1 minute or 5 minutes, neonatal intensive care unit (NICU) admission, and congenital birth defects. Contrary, Piekos et al revealed increased stillbirth risk in those with first-trimester polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection (p<0.05)⁷, while Hernández-Díaz et al measured similar risks of major congenital malformations (MCMs) in SARS-CoV-2-exposed (case group, where maternal infection was either PCR-confirmed or clinically diagnosed) and SARS-CoV-2-unexposed pregnancies (control group) (3.3% and 2.7% respectively).⁸

The impact of maternal COVID-19 infection in late pregnancy (at the second or third trimesters) is more pronounced. According to Dileep et al (in which infection of subjects was PCR-diagnosed), infection at such timing is associated with higher hospitalisation rates and more severe illness; severity then correlates positively with iatrogenic preterm delivery, lower birth weight, neonatal infection, neonatal ICU admission (p<0.001), particularly in the third trimester.[mfn referencenumber=9]9. Dileep, A et al. Sci Rep. 2022. doi:10.1038/s41598-022-07093-8.[/mfn]Preterm newborns have not yet reached full functionality, so they may encounter systemic complications like necrotising enterocolitis, acute respiratory distress syndrome, patent ductus arteriosus, retinopathy of prematurity and intraventricular haemorrhage¹⁰; preterm birth is thus unideal and should be prevented.

Maternal COVID-19 infection may also occur during the intrapartum period (at the time of labour and delivery). This is associated with higher rates of foetal death and preterm birth¹¹, with accompanying preterm complications. Intrapartum infected women may require emergency Caesarean delivery.¹² In preterm cases, this may not warrant sufficient time to accelerate pulmonary surfactant production, since dexamethasone doses are to be administered at least 4 hours apart.¹³Intrapartum COVID-19 infection also necessitates mother-newborn isolation, which may last as long as 2 weeks¹⁴, rendering breastfeeding – an activity which improves mother-newborn bonding – impossible.¹⁵

While the association between late-pregnancy COVID-19 infection and perinatal outcomes is more established, first-trimester infection studies are limited by small sample size, as evidenced by mere 17 seromolecular-diagnosed COVID-19 subjects in the study by Cosma et al. Studies mentioned in this article all defined COVID-19 infection with positive PCR diagnoses. However, some first-trimester SARS-CoV-2-positive females may only have been tested by rapid antigen tests, then postponing medical attention owing to the pandemic situation; in this case it would be more difficult to recruit first-trimester subjects. As for all trimesters, some pregnant individuals may have experienced “silent”, asymptomatic COVID-19 infections before giving birth. Therefore, these studies may only provide limited information on the impact of SARS-CoV-2 infections on pregnancy outcomes.

Another limitation of the above studies is that study findings lag behind the evolution of causative SARS-CoV-2 variants – studies on Omicron-caused COVID-infected pregnancy outcomes are ongoing and by the time results are published, the global variant of concern may already have shifted.

COVID-19 variants continue to evolve and certain variants cause greater morbidity and mortality in pregnant women, such as the alpha and delta strains.¹⁶ While it is uncertain what the next circulating strain will be, it is optimistic that previous vaccination protects individuals from severe or symptomatic illnesses by other SARS-CoV-2 strains to some extent. Meanwhile, according to the United Kingdom Obstetric Surveillance System, the percentage of moderate-to-severe illness in symptomatic COVID-19 patients reduces from 19.0% (those unvaccinated) to 5.5% (those triple-vaccinated).¹⁶ Bearing in mind that maternal COVID-19 infection severity correlates especially to third-trimester perinatal complications⁹, pregnant women or those planning to conceive should protect themselves and the foetuses through vaccination.

Overall, maternal COVID-19 infections at any trimester cause significant increases in preterm birth and neonatal intensive care unit (ICU) admission risks.^4,16The most effective way to minimise the likelihood of symptomatic maternal COVID-19 infection and foetal consequences is to receive COVID-19 vaccination.

Reference

Winchester Hospital. Available online. https://www.winchesterhospital.org/health-library/article?id=101070#:~:text=In%20the%20first%20trimester%2C%20your,to%20get%20ready%20for%20birth. Last accessed: 17 November 2022.

The American College of Obstetricians and Gynecologists. Available online. https://www.acog.org/womens-health/faqs/how-your-fetus-grows-during-pregnancy. Last accessed: 17 November 2022.

National Child & Maternal Health Education Program. Available online. https://www.nichd.nih.gov/ncmhep/initiatives/know-your-terms/moms. Last accessed: 17 November 2022.

McClymont E, et al. JAMA. 2022. doi:10.1001/jama.2022.5906.

Cosma S, et al. J Obstet Gynaecol Res. 2021. doi:10.1111/jog.15105.

Flannery DD, et al. JAMA Pediatr. 2021. doi:10.1001/jamapediatrics.2021.0038.

Piekos SN, et al. Lancet Digit Health. 2022. doi:10.1016/S2589-7500(21)00250-8.

Hernández-Díaz S, et al. Birth Defects Res. 2022. doi:10.1002/bdr2.2070.

Dileep, A et al. Sci Rep. doi:10.1038/s41598-022-07093-8.

Chee YY, et al. Hong Kong Med J. 2017. doi:10.12809/hkmj166064.

Gurol-Urganci I, et al. Am J Obstet Gynecol. 2021. doi:10.1016/j.ajog.2021.05.016.

Zlatkin, R et al. BMC Pregnancy Childbirth. doi:10.1186/s12884-022-04825-6.

Ramachandrappa A, et al. Clin Perinatol. 2008. doi:10.1016/j.clp.2008.03.006.

Sighaldeh SS & Kalan ME. J Matern Fetal Neonatal Med. 2020. doi:10.1080/14766058.2020.1777969.

Liu J, et al. Nutrients. doi:10.3390/nu6010076.

Engjom HM, et al. BMJ Medicine. 2022. doi:10.1136/bmjmed-2022-000190.

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Disclaimer

This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).